Virtual wards for people with frailty: what works, for whom, how and why-a rapid realist review.

BACKGROUND: Virtual wards (VWs) deliver multidisciplinary care at home to people with frailty who are at high risk of a crisis or in crisis, aiming to mitigate the risk of acute hospital admission. Different VW models exist, and evidence of effectiveness is inconsistent. AIM: We conducted a rapid realist review to identify different VW models and to develop explanations for how and why VWs could deliver effective frailty management. METHODS: We searched published and grey literature to identify evidence on multidisciplinary VWs. Information on how and why VWs might 'work' was extracted and synthesised into context-mechanism-outcome configurations with input from clinicians and patient/public contributors. RESULTS: We included 17 peer-reviewed and 11 grey literature documents. VWs could be short-term and acute (1-21 days), or longer-term and preventative (typically 3-7 months). Effective VW operation requires common standards agreements, information sharing processes, an appropriate multidisciplinary team that plans patient care remotely, and good co-ordination. VWs may enable delivery of frailty interventions through appropriate selection of patients, comprehensive assessment including medication review, integrated case management and proactive care. Important components for patients and caregivers are good communication with the VW, their experience of care at home, and feeling involved, safe and empowered to manage their condition. CONCLUSIONS: Insights gained from this review could inform implementation or evaluation of VWs for frailty. A combination of acute and longer-term VWs may be needed within a whole system approach. Proactive care is recommended to avoid frailty-related crises.

Interventions to prevent obesity in children aged 12 to 18 years old.

BACKGROUND: Prevention of obesity in adolescents is an international public health priority. The prevalence of overweight and obesity is over 25% in North and South America, Australia, most of Europe, and the Gulf region. Interventions that aim to prevent obesity involve strategies that promote healthy diets or 'activity' levels (physical activity, sedentary behaviour and/or sleep) or both, and work by reducing energy intake and/or increasing energy expenditure, respectively. There is uncertainty over which approaches are more effective, and numerous new studies have been published over the last five years since the previous version of this Cochrane Review. OBJECTIVES: To assess the effects of interventions that aim to prevent obesity in adolescents by modifying dietary intake or 'activity' levels, or a combination of both, on changes in BMI, zBMI score and serious adverse events. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was February 2023. SELECTION CRITERIA: Randomised controlled trials in adolescents (mean age 12 years and above but less than 19 years), comparing diet or 'activity' interventions (or both) to prevent obesity with no intervention, usual care, or with another eligible intervention, in any setting. Studies had to measure outcomes at a minimum of 12 weeks post baseline. We excluded interventions designed primarily to improve sporting performance. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our outcomes were BMI, zBMI score and serious adverse events, assessed at short- (12 weeks to < 9 months from baseline), medium- (9 months to < 15 months) and long-term (≥ 15 months) follow-up. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: This review includes 74 studies (83,407 participants); 54 studies (46,358 participants) were included in meta-analyses. Sixty studies were based in high-income countries. The main setting for intervention delivery was schools (57 studies), followed by home (nine studies), the community (five studies) and a primary care setting (three studies). Fifty-one interventions were implemented for less than nine months; the shortest was conducted over one visit and the longest over 28 months. Sixty-two studies declared non-industry funding; five were funded in part by industry. Dietary interventions versus control The evidence is very uncertain about the effects of dietary interventions on body mass index (BMI) at short-term follow-up (mean difference (MD) -0.18, 95% confidence interval (CI) -0.41 to 0.06; 3 studies, 605 participants), medium-term follow-up (MD -0.65, 95% CI -1.18 to -0.11; 3 studies, 900 participants), and standardised BMI (zBMI) at long-term follow-up (MD -0.14, 95% CI -0.38 to 0.10; 2 studies, 1089 participants); all very low-certainty evidence. Compared with control, dietary interventions may have little to no effect on BMI at long-term follow-up (MD -0.30, 95% CI -1.67 to 1.07; 1 study, 44 participants); zBMI at short-term (MD -0.06, 95% CI -0.12 to 0.01; 5 studies, 3154 participants); and zBMI at medium-term (MD 0.02, 95% CI -0.17 to 0.21; 1 study, 112 participants) follow-up; all low-certainty evidence. Dietary interventions may have little to no effect on serious adverse events (two studies, 377 participants; low-certainty evidence). Activity interventions versus control Compared with control, activity interventions do not reduce BMI at short-term follow-up (MD -0.64, 95% CI -1.86 to 0.58; 6 studies, 1780 participants; low-certainty evidence) and probably do not reduce zBMI at medium- (MD 0, 95% CI -0.04 to 0.05; 6 studies, 5335 participants) or long-term (MD -0.05, 95% CI -0.12 to 0.02; 1 study, 985 participants) follow-up; both moderate-certainty evidence. Activity interventions do not reduce zBMI at short-term follow-up (MD 0.02, 95% CI -0.01 to 0.05; 7 studies, 4718 participants; high-certainty evidence), but may reduce BMI slightly at medium-term (MD -0.32, 95% CI -0.53 to -0.11; 3 studies, 2143 participants) and long-term (MD -0.28, 95% CI -0.51 to -0.05; 1 study, 985 participants) follow-up; both low-certainty evidence. Seven studies (5428 participants; low-certainty evidence) reported data on serious adverse events: two reported injuries relating to the exercise component of the intervention and five reported no effect of intervention on reported serious adverse events. Dietary and activity interventions versus control Dietary and activity interventions, compared with control, do not reduce BMI at short-term follow-up (MD 0.03, 95% CI -0.07 to 0.13; 11 studies, 3429 participants; high-certainty evidence), and probably do not reduce BMI at medium-term (MD 0.01, 95% CI -0.09 to 0.11; 8 studies, 5612 participants; moderate-certainty evidence) or long-term (MD 0.06, 95% CI -0.04 to 0.16; 6 studies, 8736 participants; moderate-certainty evidence) follow-up. They may have little to no effect on zBMI in the short term, but the evidence is very uncertain (MD -0.09, 95% CI -0.2 to 0.02; 3 studies, 515 participants; very low-certainty evidence), and they may not reduce zBMI at medium-term (MD -0.05, 95% CI -0.1 to 0.01; 6 studies, 3511 participants; low-certainty evidence) or long-term (MD -0.02, 95% CI -0.05 to 0.01; 7 studies, 8430 participants; low-certainty evidence) follow-up. Four studies (2394 participants) reported data on serious adverse events (very low-certainty evidence): one reported an increase in weight concern in a few adolescents and three reported no effect. AUTHORS' CONCLUSIONS: The evidence demonstrates that dietary interventions may have little to no effect on obesity in adolescents. There is low-certainty evidence that activity interventions may have a small beneficial effect on BMI at medium- and long-term follow-up. Diet plus activity interventions may result in little to no difference. Importantly, this updated review also suggests that interventions to prevent obesity in this age group may result in little to no difference in serious adverse effects. Limitations of the evidence include inconsistent results across studies, lack of methodological rigour in some studies and small sample sizes. Further research is justified to investigate the effects of diet and activity interventions to prevent childhood obesity in community settings, and in young people with disabilities, since very few ongoing studies are likely to address these. Further randomised trials to address the remaining uncertainty about the effects of diet, activity interventions, or both, to prevent childhood obesity in schools (ideally with zBMI as the measured outcome) would need to have larger samples.

Interventions to prevent obesity in children aged 5 to 11 years old.

BACKGROUND: Prevention of obesity in children is an international public health priority given the prevalence of the condition (and its significant impact on health, development and well-being). Interventions that aim to prevent obesity involve behavioural change strategies that promote healthy eating or 'activity' levels (physical activity, sedentary behaviour and/or sleep) or both, and work by reducing energy intake and/or increasing energy expenditure, respectively. There is uncertainty over which approaches are more effective and numerous new studies have been published over the last five years, since the previous version of this Cochrane review. OBJECTIVES: To assess the effects of interventions that aim to prevent obesity in children by modifying dietary intake or 'activity' levels, or a combination of both, on changes in BMI, zBMI score and serious adverse events. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was February 2023. SELECTION CRITERIA: Randomised controlled trials in children (mean age 5 years and above but less than 12 years), comparing diet or 'activity' interventions (or both) to prevent obesity with no intervention, usual care, or with another eligible intervention, in any setting. Studies had to measure outcomes at a minimum of 12 weeks post baseline. We excluded interventions designed primarily to improve sporting performance. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our outcomes were body mass index (BMI), zBMI score and serious adverse events, assessed at short- (12 weeks to < 9 months from baseline), medium- (9 months to < 15 months) and long-term (≥ 15 months) follow-up. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: This review includes 172 studies (189,707 participants); 149 studies (160,267 participants) were included in meta-analyses. One hundred forty-six studies were based in high-income countries. The main setting for intervention delivery was schools (111 studies), followed by the community (15 studies), the home (eight studies) and a clinical setting (seven studies); one intervention was conducted by telehealth and 31 studies were conducted in more than one setting. Eighty-six interventions were implemented for less than nine months; the shortest was conducted over one visit and the longest over four years. Non-industry funding was declared by 132 studies; 24 studies were funded in part or wholly by industry. Dietary interventions versus control Dietary interventions, compared with control, may have little to no effect on BMI at short-term follow-up (mean difference (MD) 0, 95% confidence interval (CI) -0.10 to 0.10; 5 studies, 2107 participants; low-certainty evidence) and at medium-term follow-up (MD -0.01, 95% CI -0.15 to 0.12; 9 studies, 6815 participants; low-certainty evidence) or zBMI at long-term follow-up (MD -0.05, 95% CI -0.10 to 0.01; 7 studies, 5285 participants; low-certainty evidence). Dietary interventions, compared with control, probably have little to no effect on BMI at long-term follow-up (MD -0.17, 95% CI -0.48 to 0.13; 2 studies, 945 participants; moderate-certainty evidence) and zBMI at short- or medium-term follow-up (MD -0.06, 95% CI -0.13 to 0.01; 8 studies, 3695 participants; MD -0.04, 95% CI -0.10 to 0.02; 9 studies, 7048 participants; moderate-certainty evidence). Five studies (1913 participants; very low-certainty evidence) reported data on serious adverse events: one reported serious adverse events (e.g. allergy, behavioural problems and abdominal discomfort) that may have occurred as a result of the intervention; four reported no effect. Activity interventions versus control Activity interventions, compared with control, may have little to no effect on BMI and zBMI at short-term or long-term follow-up (BMI short-term: MD -0.02, 95% CI -0.17 to 0.13; 14 studies, 4069 participants; zBMI short-term: MD -0.02, 95% CI -0.07 to 0.02; 6 studies, 3580 participants; low-certainty evidence; BMI long-term: MD -0.07, 95% CI -0.24 to 0.10; 8 studies, 8302 participants; zBMI long-term: MD -0.02, 95% CI -0.09 to 0.04; 6 studies, 6940 participants; low-certainty evidence). Activity interventions likely result in a slight reduction of BMI and zBMI at medium-term follow-up (BMI: MD -0.11, 95% CI -0.18 to -0.05; 16 studies, 21,286 participants; zBMI: MD -0.05, 95% CI -0.09 to -0.02; 13 studies, 20,600 participants; moderate-certainty evidence). Eleven studies (21,278 participants; low-certainty evidence) reported data on serious adverse events; one study reported two minor ankle sprains and one study reported the incident rate of adverse events (e.g. musculoskeletal injuries) that may have occurred as a result of the intervention; nine studies reported no effect. Dietary and activity interventions versus control Dietary and activity interventions, compared with control, may result in a slight reduction in BMI and zBMI at short-term follow-up (BMI: MD -0.11, 95% CI -0.21 to -0.01; 27 studies, 16,066 participants; zBMI: MD -0.03, 95% CI -0.06 to 0.00; 26 studies, 12,784 participants; low-certainty evidence) and likely result in a reduction of BMI and zBMI at medium-term follow-up (BMI: MD -0.11, 95% CI -0.21 to 0.00; 21 studies, 17,547 participants; zBMI: MD -0.05, 95% CI -0.07 to -0.02; 24 studies, 20,998 participants; moderate-certainty evidence). Dietary and activity interventions compared with control may result in little to no difference in BMI and zBMI at long-term follow-up (BMI: MD 0.03, 95% CI -0.11 to 0.16; 16 studies, 22,098 participants; zBMI: MD -0.02, 95% CI -0.06 to 0.01; 22 studies, 23,594 participants; low-certainty evidence). Nineteen studies (27,882 participants; low-certainty evidence) reported data on serious adverse events: four studies reported occurrence of serious adverse events (e.g. injuries, low levels of extreme dieting behaviour); 15 studies reported no effect. Heterogeneity was apparent in the results for all outcomes at the three follow-up times, which could not be explained by the main setting of the interventions (school, home, school and home, other), country income status (high-income versus non-high-income), participants' socioeconomic status (low versus mixed) and duration of the intervention. Most studies excluded children with a mental or physical disability. AUTHORS' CONCLUSIONS: The body of evidence in this review demonstrates that a range of school-based 'activity' interventions, alone or in combination with dietary interventions, may have a modest beneficial effect on obesity in childhood at short- and medium-term, but not at long-term follow-up. Dietary interventions alone may result in little to no difference. Limited evidence of low quality was identified on the effect of dietary and/or activity interventions on severe adverse events and health inequalities; exploratory analyses of these data suggest no meaningful impact. We identified a dearth of evidence for home and community-based settings (e.g. delivered through local youth groups), for children living with disabilities and indicators of health inequities.

Dexamethasone doses in patients with COVID-19 and hypoxia: A systematic review and meta-analysis.

BACKGROUND: The optimal dose of dexamethasone for severe/critical COVID-19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID-19 and hypoxia. METHODS: We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethasone in adults with COVID-19 and hypoxia. The primary outcome was mortality at 1 month. Secondary outcomes were mortality closest to 90 days; days alive without life support; and the occurrence of serious adverse events/reactions (SAEs/SARs) closest to 1 month. We assessed the risk of bias using the Cochrane RoB2 tool, risk of random errors using trial sequential analysis, and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included eight trials (2478 participants), of which four (1293 participants) had low risk of bias. Higher doses of dexamethasone probably resulted in little to no difference in mortality at 1 month (relative risk [RR] 0.97, 95% CI: 0.79-1.19), mortality closest to Day 90 (RR 1.01, 95% CI: 0.86-1.20), and SAEs/SARs (RR 1.00, 95% CI: 0.97-1.02). Higher doses of dexamethasone probably increased the number of days alive without invasive mechanical ventilation and circulatory support but had no effect on days alive without renal replacement therapy. CONCLUSIONS: Based on low to moderate certainty evidence, higher versus standard doses of dexamethasone probably result in little to no difference in mortality, SAEs/SARs, and days alive without renal replacement therapy, but probably increase the number of days alive without invasive mechanical ventilation and circulatory support.

Factors associated with repeat emergency department visits for mental health care in adolescents: A scoping review.

OBJECTIVES: The aim of this review was to identify factors associated with multiple visits to emergency department (ED) services for mental health care in adolescents. METHODS: Electronic databases (MEDLINE, PsycINFO, Embase, CINAHL, Web of Science and ProQuest Dissertations & Thesis Global) were searched for evidence that presented an association between risk factors or correlates of multiple visits to the emergency departmental for mental health care by 10-24 year olds. High impact use was defined as at least one return ED visit for mental health care. Primary studies of any quantitative design were included, with no exclusions based on language or country and all possible risk factors were considered. Data were extracted and synthesised using quantitative methods; frequencies of positive, negative and null associations were summarised for categories of potential risk factors. RESULTS: Sixty-five studies were included in the review. Most studies were from North America and reported a wide range of measures of high impact ED use, the most common being a binary indicator of multiple ED visits. Sex/gender and age were the most frequently reported risk factors. Measure of previous or concurrent access to mental health care was consistently positively associated with high impact use. Having private health insurance, compared with public or no insurance, was generally negatively associated with high impact use. Proxy measures of socioeconomic position (SEP) showed associations between lower SEP and more high impact use in a small number of studies. No other factors were consistently or uniformly associated with high impact use. CONCLUSIONS: The review identified a substantial evidence base but due to the variability in study design and measurement of both risk factors and outcomes, no consistent risk factors emerged. More research is needed, particularly outside North America, using robust methods and high quality routinely collected data.

The positive and negative consequences of stress and its relationship with coping in medical students: A qualitative study.

Rates of mental health problems among medical students have prompted efforts to reduce stress during medical training. However, stress can be motivating and is a feature of clinical work. This qualitative study explores what makes an experience stressful, and how medical students respond to such experiences. In-depth interviews were conducted with a purposive sample of 15 medical students. Experiences were distressing when they threatened students' self-perception, goals or coping mechanisms, or when they reminded the student of distressing past events. Moderate stress was motivating and could build resilience. Students selected coping mechanisms based on their availability, acceptability, likely outcome and their previous experience of using these mechanisms. Social support, extra-curricular activities and exercise were helpful. High levels of distress, poor self-esteem and course factors, including remote placements, impaired engagement with coping strategies. Perception of stressors as being insurmountable or beyond one's control, led to increasing distress and the adoption of avoidant coping strategies. University strategies need to consider the beneficial effects of stress and seek to bolster coping resources as well as minimising unnecessary sources of stress.

Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1.

Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.

Does immediate dentin sealing influence postoperative sensitivity in teeth restored with indirect restorations? A systematic review and meta-analysis.

OBJECTIVE: This study comprehensively reviewed clinical trials that investigated the effect of immediate dentin sealing (IDS) technique on postoperative sensitivity (POS) and clinical performance of indirect restorations. MATERIALS AND METHODS: The systematic review was conducted according to the preferred reporting items for systematic reviews and meta-analyses statement, and was guided by the PICOS strategy. Clinical trials in which adult patients received at least one indirect restoration cemented with IDS approach and one restoration cemented following the delayed dentin sealing (DDS) were considered. RESULTS: Following title screening and full-text reading, four studies met the inclusion criteria and were included for qualitative synthesis, while two studies were selected for quantitative synthesis. According to Risk of bias-2 tool, two studies were classified as "some concerns" for the outcome POS. No statistically significant differences were found between teeth restored with indirect restorations using the IDS and DDS approach for POS (p > 0.05), neither at the baseline (very low certainty of evidence according to GRADE) nor after 2 years of follow-up (low certainty of evidence according to GRADE). CONCLUSION: There is low-certainty evidence that IDS does not reduce POS in teeth restored with indirect restorations. CLINICAL SIGNIFICANCE: There is no clinical evidence to favor IDS over DDS when restoring teeth with indirect restorations.

Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis.

Importance: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm. Objective: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes. Data Sources: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts. Study Selection: Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria. Data Extraction and Synthesis: In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality. Main Outcomes and Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days. Results: A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16). Conclusions and Relevance: In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality. Trial Registration: PROSPERO Identifier: CRD42021230155.

Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis.

Importance: Effective therapies for patients with coronavirus disease 2019 (COVID-19) are needed, and clinical trial data have demonstrated that low-dose dexamethasone reduced mortality in hospitalized patients with COVID-19 who required respiratory support. Objective: To estimate the association between administration of corticosteroids compared with usual care or placebo and 28-day all-cause mortality. Design, Setting, and Participants: Prospective meta-analysis that pooled data from 7 randomized clinical trials that evaluated the efficacy of corticosteroids in 1703 critically ill patients with COVID-19. The trials were conducted in 12 countries from February 26, 2020, to June 9, 2020, and the date of final follow-up was July 6, 2020. Pooled data were aggregated from the individual trials, overall, and in predefined subgroups. Risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effect meta-analysis of overall mortality, with the association between the intervention and mortality quantified using odds ratios (ORs). Random-effects meta-analyses also were conducted (with the Paule-Mandel estimate of heterogeneity and the Hartung-Knapp adjustment) and an inverse variance-weighted fixed-effect analysis using risk ratios. Exposures: Patients had been randomized to receive systemic dexamethasone, hydrocortisone, or methylprednisolone (678 patients) or to receive usual care or placebo (1025 patients). Main Outcomes and Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. A secondary outcome was investigator-defined serious adverse events. Results: A total of 1703 patients (median age, 60 years [interquartile range, 52-68 years]; 488 [29%] women) were included in the analysis. Risk of bias was assessed as "low" for 6 of the 7 mortality results and as "some concerns" in 1 trial because of the randomization method. Five trials reported mortality at 28 days, 1 trial at 21 days, and 1 trial at 30 days. There were 222 deaths among the 678 patients randomized to corticosteroids and 425 deaths among the 1025 patients randomized to usual care or placebo (summary OR, 0.66 [95% CI, 0.53-0.82]; P < .001 based on a fixed-effect meta-analysis). There was little inconsistency between the trial results (I2 = 15.6%; P = .31 for heterogeneity) and the summary OR was 0.70 (95% CI, 0.48-1.01; P = .053) based on the random-effects meta-analysis. The fixed-effect summary OR for the association with mortality was 0.64 (95% CI, 0.50-0.82; P < .001) for dexamethasone compared with usual care or placebo (3 trials, 1282 patients, and 527 deaths), the OR was 0.69 (95% CI, 0.43-1.12; P = .13) for hydrocortisone (3 trials, 374 patients, and 94 deaths), and the OR was 0.91 (95% CI, 0.29-2.87; P = .87) for methylprednisolone (1 trial, 47 patients, and 26 deaths). Among the 6 trials that reported serious adverse events, 64 events occurred among 354 patients randomized to corticosteroids and 80 events occurred among 342 patients randomized to usual care or placebo. Conclusions and Relevance: In this prospective meta-analysis of clinical trials of critically ill patients with COVID-19, administration of systemic corticosteroids, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.

Association Between Risk-of-Bias Assessments and Results of Randomized Trials in Cochrane Reviews: The ROBES Meta-Epidemiologic Study.

Flaws in the design of randomized trials may bias intervention effect estimates and increase between-trial heterogeneity. Empirical evidence suggests that these problems are greatest for subjectively assessed outcomes. For the Risk of Bias in Evidence Synthesis (ROBES) Study, we extracted risk-of-bias judgements (for sequence generation, allocation concealment, blinding, and incomplete data) from a large collection of meta-analyses published in the Cochrane Library (issue 4; April 2011). We categorized outcome measures as mortality, other objective outcome, or subjective outcome, and we estimated associations of bias judgements with intervention effect estimates using Bayesian hierarchical models. Among 2,443 randomized trials in 228 meta-analyses, intervention effect estimates were, on average, exaggerated in trials with high or unclear (versus low) risk-of-bias judgements for sequence generation (ratio of odds ratios (ROR) = 0.91, 95% credible interval (CrI): 0.86, 0.98), allocation concealment (ROR = 0.92, 95% CrI: 0.86, 0.98), and blinding (ROR = 0.87, 95% CrI: 0.80, 0.93). In contrast to previous work, we did not observe consistently different bias for subjective outcomes compared with mortality. However, we found an increase in between-trial heterogeneity associated with lack of blinding in meta-analyses with subjective outcomes. Inconsistency in criteria for risk-of-bias judgements applied by individual reviewers is a likely limitation of routinely collected bias assessments. Inadequate randomization and lack of blinding may lead to exaggeration of intervention effect estimates in randomized trials.

Interventions for preventing or treating malnutrition in homeless problem-drinkers: a systematic review.

BACKGROUND: Excessive drinking leads to poor absorption of nutrients and homeless problem-drinkers often have nutritionally inadequate diets. Depletion of nutrients such as vitamin B1 can lead to cognitive impairment, which can hinder efforts to reduce drinking or engage with services. This review aimed to assess effectiveness of interventions designed to prevent or treat malnutrition in homeless problem-drinkers. METHODS: We systematically searched nine electronic databases and 13 grey literature sources for studies evaluating interventions to improve nutrition in homeless populations, without regional or language restrictions. Screening for inclusion was done in duplicate. One reviewer extracted data and assessed risk of bias, and another checked the extractions. Primary outcomes were nutrition status/deficiency, liver damage, and cognitive function. Secondary outcomes included abstinence, comorbidities, resource use, acceptability and engagement with intervention. Results were synthesised narratively. RESULTS: We included 25 studies (2 Randomised Controlled Trials; 15 uncontrolled before and after; 7 surveys; 1 case-control). Nine studies evaluated educational and support interventions, five food provision, and three supplement provision. Eight studies evaluated a combination of these interventions. No two interventions were the same, and all studies were at high risk of bias. Nutritional status (intake/ deficiency) were reported in 11 studies and liver function in one. Fruit and vegetable intake improved with some education and support interventions (n = 4 studies) but not others (n = 2). Vitamin supplements appeared to improve vitamin deficiency levels in the blood (n = 2). Free or subsidised meals (n = 4) and food packs (n = 1) did not always fulfil dietary needs, but were usually considered acceptable by users. Some multicomponent interventions improved nutrition (n = 3) but acceptability varied (n = 3). No study reported cost effectiveness. CONCLUSIONS: The evidence for any one intervention for improving malnutrition in homeless problem-drinkers was based on single studies at high risk of bias. Various food and supplement provision interventions appear effective in changing nutritional status in single studies. Educational and multicomponent interventions show improved nutritional behaviour in some studies but not others. Further better quality evidence is required before these interventions can be recommended for implementation. Any future studies should seek the end user input in their design and conduct. TRIAL REGISTRATION: Registered with PROSPERO: CRD42015024247 .

Antipsychotic polypharmacy and metabolic syndrome in schizophrenia: a review of systematic reviews.

BACKGROUND: There is conflicting evidence on the association between antipsychotic polypharmacy and metabolic syndrome in schizophrenia. We conducted a review of published systematic reviews to evaluate evidence on the association between metabolic syndrome (diabetes, hypertension, and hyperlipidaemia) and exposure to antipsychotic polypharmacy in schizophrenia. METHODS: We searched five electronic databases, complemented by reference screening, to find systematic reviews that investigated the association of antipsychotic polypharmacy in schizophrenia with hypertension, diabetes, or hyperlipidaemia. Selection of reviews, data extraction and review quality were conducted independently by two people and disagreements resolved by discussion. Results were synthesised narratively. RESULTS: We included 12 systematic reviews, which reported heterogeneous results, mostly with narrative syntheses and without pooled data. The evidence was rated as low quality. There was some indication of a possible protective effect of drug combinations including aripiprazole for diabetes and hyperlipidaemias, compared to other combinations and/or monotherapy. Only one review reported the association between APP and hypertension. The most frequently reported combinations of medication included clozapine, possibly representing a sample of patients with treatment resistant illness. No included review reported results separately by setting (primary or secondary care). CONCLUSIONS: Further robust studies are needed to elucidate the possible protective effect of aripiprazole. Long-term prospective studies are required for accurate appraisal of diabetes risk, hypertension and hyperlipidaemia in patients exposed to antipsychotic polypharmacy.

Nutritional deficiencies in homeless persons with problematic drinking: a systematic review.

BACKGROUND: A significant proportion of homeless people drink alcohol excessively and this can lead to malnutrition and consequent medical problems. The aim of this review was to assess the evidence on the range of nutritional deficiencies in the homeless problem-drinking populations. METHODS: We conducted a comprehensive search of nine scientific literature databases and 13 grey literature sources. We included studies of any design that included homeless population with problem-drinking and reported measures of nutritional deficiencies in urine or blood. Study selection and data extraction was done by one reviewer and checked by another. Data on malnutrition profile were summarized narratively. RESULTS: We found nine studies reporting nutritional deficiencies in homeless populations with problem-drinking. The oldest study was from the 1950s and the most recent from 2013. The following nutrients were reported across studies: vitamins B1, B2, B6, B9, B12, C, A, and E; haemoglobin; and albumin. The most common deficiencies reported were of vitamin B1 (prevalence of deficiency was 0, 2, 6, 45, and 51% in five studies) and vitamin C (29, 84, and 95% in three studies). None of the studies were assessed to be at a low risk of bias. CONCLUSIONS: The limited, low quality and relatively old evidence suggests that homeless people who drink heavily may be deficient in vitamin C, thiamine, and other nutrients. New, well conducted studies are needed in order to optimally inform public health interventions aimed at improving deficiencies in this population. TRIAL REGISTRATION: PROSPERO CRD42015024247.

What are important outcomes of bariatric surgery? An in-depth analysis to inform the development of a core outcome set and a comparison between the views of surgeons and other health professionals (the BARIACT study).

BACKGROUND: Outcome reporting in bariatric surgery needs uniformity. A core outcome set is an agreed minimum set of outcomes reported in all studies of a particular condition, but members of the bariatric multidisciplinary team might value outcomes differently. The aim of this study was to summarise existing outcome reporting in bariatric surgery, to inform the development of a core outcome set, and to compare outcomes selected as important by type of health professional. METHODS: Outcomes reported in randomised controlled trials (RCTs) and large non-randomised studies, identified by a systematic review, were listed verbatim. Frequency of outcome reporting and uniformity of definition were assessed. A questionnaire to rate the importance of each outcome was completed by members of the bariatric multidisciplinary team. Responses to each item were scored as 1 (not essential) to 9 (absolutely essential). We ranked outcomes according to percentage deemed important (7-9) and according to respondents by type of health professional. FINDINGS: We identified 1088 individual outcomes from 90 studies (39 RCTs), grouped them into health domains, and presented them as a questionnaire with 131 items to 489 multidisciplinary team members. Most outcomes (n=920, 85%) were reported only once. The largest outcome domain was surgical complications, and 432 outcomes (42%) corresponded to an adverse event. Only a quarter of outcomes (n=461) were defined, and were often contradictory. For questionnaire responders (n=164, response rate 33·5%), most were surgeons (n=80, 48·8%), followed by dietitians (n=31, 18·9%), nurses (n=24, 14·6%), physicians (n=12, 7·3%), and others (n=16, 9·9%). Improvement in diabetes was the top outcome for all health professionals. Seven of the surgeon's top ten outcomes were adverse events, compared with three for other health professionals. Groups valued a measure of weight differently (third vs 15th for other health professionals and surgeons, respectively). INTERPRETATION: This study shows that the assessment of bariatric surgery focuses largely on adverse events and resolution of comorbidity, but that reporting is inconsistent and ill-defined. Substantial variation between the views of surgeons and those of other health professionals was evident. The next step is to provide feedback to participants and to survey their views again before a final consensus meeting to produce a core outcome set for the Benefits and Adverse events in BARIAtric surgery Clinical Trials (BARIACT) as a solution to this problem. FUNDING: National Institute for Health Research (NIHR), and the NIHR Health Technology Assessment programme. This work was also undertaken with the support of the MRC ConDuCT-II Hub (Collaboration and innovation for Difficult and Complex randomised controlled Trials In Invasive procedures, MR/K025643/1).

Symptomatic and quality-of-life outcomes after treatment for clinically localised prostate cancer: a systematic review.

To conduct a systematic review of the risks of short-term outcomes after major treatments for clinically localised prostate cancer. MEDLINE, EMBASE and the Cochrane Library were searched from 2004 to January 2013. Study arms that included ≥100 men with localised prostate cancer in receipt of surgery, radiotherapy or active surveillance and reported symptomatic and quality-of-life (QoL) data from 6 to 60 months after treatment were eligible. Data were extracted by one reviewer and checked by another. In all, 64 studies (80 treatment cohorts) were included. Most were single treatment cohorts from the USA or Europe. Radiotherapy was the most common treatment (40 cohorts, including 31 brachytherapy cohorts) followed by prostatectomy (39 cohorts), with only one active surveillance cohort. Most frequently measured symptoms were urinary, followed by sexual, and bowel; QoL was assessed in only 17 cohorts. Most studies used validated measures, although poor data reporting and differences between studies meant that it was not possible to pool data. Data on the precise impact of short-term symptomatic and QoL outcomes after treatment for localised prostate cancer are of insufficient quality for clear guidance to men about the risks to these aspects of their lives. It is important that future studies focus on collecting core outcomes through validated measures and comply with reporting guidelines, so that clear and accurate information can be derived for men considering screening or treatment for prostate cancer.

A Systematic Review of Patient-reported Outcomes in Randomized Controlled Trials of Unplanned General Surgery.

Unplanned general surgery represents a major workload and requires comprehensive evaluation with appropriate outcomes. This study aimed to summarize current reporting of patient-reported outcomes (PROs) in randomized clinical trials (RCTs) in unplanned general surgery. A systematic review identified RCTs reporting PROs in the commonest six areas of unplanned general surgery. Details of the PRO measures were examined using the CONSORT extension for PRO reporting in RCTs. Extracted information about each PRO domain included the reporting of baseline PROs, rationale for PRO selection and whether PRO findings were used in conjunction with clinical outcomes to inform treatment recommendations. The internal validity of included studies was assessed using the Cochrane risk of bias tool. 12,519 abstracts were screened and 20 RCTs containing data from 2037 patients included. Included studies used 14 separate PRO measures covering 35 different health domains. A visual analogue assessment of pain was most frequently reported (n = 13). Reporting of baseline PRO data was uncommon (11/35 PRO domains). The rationale for PRO data collection and a PRO-specific hypothesis were provided for 9 (25.7 %) and 5 (14.3 %) domains, respectively. Seventeen RCTs (85.0 %) used the PRO data alongside clinical outcomes to inform treatment recommendations. Of the 116 risk of bias assessments, 77 (66.0 %) were judged as high or unclear. There is a lack of well designed, and conducted RCTs in unplanned general surgery that include PROs. Future work to define relevant PROs and methods for optimal assessment are needed to inform health care decision-making.

Overall survival after mastectomy versus breast-conserving surgery with adjuvant radiotherapy for early-stage breast cancer: meta-analysis.

BACKGROUND: Breast-conserving surgery with adjuvant radiotherapy and mastectomy are currently offered as equivalent surgical options for early-stage breast cancer based on RCTs from the 1970s and 1980s. However, the treatment of breast cancer has evolved and recent observational studies suggest a survival advantage for breast-conserving surgery with adjuvant radiotherapy. A systematic review and meta-analysis was undertaken to summarize the contemporary evidence regarding survival after breast-conserving surgery with adjuvant radiotherapy versus mastectomy for women with early-stage breast cancer. METHODS: A systematic search of MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase that identified studies published between 1 January 2000 and 18 December 2023 comparing overall survival after breast-conserving surgery with adjuvant radiotherapy versus mastectomy for patients with unilateral stage 1-3 breast cancer was undertaken. The main exclusion criteria were studies evaluating neoadjuvant chemotherapy, rare breast cancer subtypes, and specific breast cancer populations. The ROBINS-I tool was used to assess risk of bias, with the overall certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. Studies without critical risk of bias were included in a quantitative meta-analysis. RESULTS: From 11 750 abstracts, 108 eligible articles were identified, with one article including two studies; 29 studies were excluded from the meta-analysis due to an overall critical risk of bias, 42 studies were excluded due to overlapping study populations, and three studies were excluded due to reporting incompatible results. A total of 35 observational studies reported survival outcomes for 909 077 patients (362 390 patients undergoing mastectomy and 546 687 patients undergoing breast-conserving surgery with adjuvant radiotherapy). The pooled HR was 0.72 (95% c.i. 0.68 to 0.75, P < 0.001), demonstrating improved overall survival for patients undergoing breast-conserving surgery with adjuvant radiotherapy. The overall certainty of the evidence was very low. CONCLUSION: This meta-analysis provides evidence suggesting a survival advantage for women undergoing breast-conserving surgery with adjuvant radiotherapy for early-stage breast cancer compared with mastectomy. Although these results should be interpreted with caution, they should be shared with patients to support informed surgical decision-making.

Systematic review and meta-analysis of the accuracy of McIsaac and Centor score in patients presenting to secondary care with pharyngitis.

BACKGROUND: Centor and McIsaac scores are clinical prediction rules for diagnosing group A streptococcus (GAS) infection in patients with pharyngitis. Their recommended thresholds vary between guidelines. OBJECTIVES: To estimate the sensitivity and specificity of the McIsaac and Centor scores to diagnose GAS pharyngitis and evaluate their impact on antibiotic prescribing at each threshold in patients presenting to secondary care. DATA SOURCES: MEDLINE, Embase, and Web of Science were searched from inception to September 2022. STUDY ELIGIBILITY CRITERIA: Studies of patients presenting with acute pharyngitis to emergency or outpatient clinics that estimated the accuracy of McIsaac or Centor scores against throat cultures and/or rapid antigen detection tests (RADT) as reference standards. TESTS: Centor or McIsaac score. REFERENCE STANDARD: Throat cultures and/or RADT. ASSESSMENT OF RISK OF BIAS: Quality Assessment of Diagnostic Accuracy Studies. METHODS OF DATA SYNTHESIS: The sensitivities and specificities of the McIsaac and Centor scores were pooled at each threshold using bivariate random effects meta-analysis. RESULTS: Fourteen studies were included (eight McIsaac and six Centor scores). Eight studies had unclear and six had a high risk of bias. The McIsaac score had higher estimated sensitivity and lower specificity relative to Centor scores at equivalent thresholds but with wide and overlapping confidence regions. Using either score as a triage to RADT to decide antibiotic treatment would reduce antibiotic prescription to patients with non-GAS pharyngitis relative to RADT test for everyone, but also reduce antibiotic prescription to patients with GAS. DISCUSSION: Centor and McIsaac scores are equally ineffective at triaging patients who need antibiotics presenting with pharyngitis at hospitals. At high thresholds, too many true positive cases are missed, whereas at low thresholds, too many false positives are treated, leading to the over prescription of antibiotics. The former may be compensated by adequate safety netting by clinicians, ensuring that patients can seek help if symptoms worsen.

Prognostic models for clinical outcomes in patients with venous leg ulcers: A systematic review.

OBJECTIVE: The purpose of this review was to identify prognostic models for clinical application in patients with venous leg ulcers (VLUs). METHODS: Literature searches were conducted in Embase, Medline, Cochrane, and CINAHL databases from inception to December 22, 2021. Eligible studies reported prognostic models aimed at developing, validating, and adjusting multivariable prognostic models that include multiple prognostic factors combined, and that predicted clinical outcomes. Methodological quality was assessed using the CHARMS checklist and PROBAST short form questionnaire. RESULTS: Thirteen studies were identified, of which three were validation studies of previously published models, four reported derivation and validation of models, and the remainder reported derivation models only. There was substantial heterogeneity in the model characteristics, including 11 studies focused on wound healing outcomes reporting 91 different predictors. Three studies shared similar predicted outcomes, follow-up timepoint and used a Cox proportional hazards model. However, these models reported different predictor selection methods and different predictors and it was therefore not feasible to summarize performance, such as discriminative ability. CONCLUSIONS: There are no standout risk prediction models in the literature with promising clinical application for patients with VLUs. Future research should focus on developing and validating high-performing models in wider VLU populations.